A 2-dimensional (2D) microcapillary HPLC-tandem mass spectrometer (2D mu LC-MS/MS) will be purchased and used to support the research of a multidisciplinary group of 10 major NIH-funded projects (including several multi-investigator program projects) and 5 minor users. Approximately 80% of the instrument time will be utilized by NIH-funded major users, and the remaining 20% of the time will be used by the minor users and new users from on campus or in the Chicago area. This instrument will complement the MALDI TOF mass spectrometer that is already devoted to proteomics research within the Research Resources Center (RRC) of the University of Illinois at Chicago and will provide unique microcapillary HPLC capabilities and on-line solution phase protein characterization and identification. In particular this instrument will be used by many NIH-funded investigators for proteomic profiling using techniques such as isotope-coded affinity tags (ICAT). Presently, our investigators must seek collaborators at other institutions for such studies, since there are no comparable proteomics instruments available on campus. The proposed instrument will be located on the medical campus of the University of Illinois at Chicago in recently renovated space under the supervision of the P.I. Access to the instrument by new users on and off campus will be assured through the administrative oversight of an advisory committee appointed by the RRC which is a centralized campus instrumentation facility that has been in operation for over 50 years. The RRC recently hired a Ph.D. level senior mass spectrometrist to oversee the MALDI TOP mass spectrometer, and a new proteomics mass spectrometrist will be recruited to operate and maintain the proposed 2D LC-MS/MS system and carry out ICAT and similar analyses. These positions are committed for at least the useful lifetimes of these proteomics instruments. Furthermore, the Mass Spectrometry Laboratory is under the oversight of the P.I. Dr. Richard B. van Breemen, who has more than 20 years of experience in biomedical mass spectrometry. These on-going personnel commitments represent substantial support by the RRC and the university. User fees (determined by the advisory committee) will be collected to defray the costs of consumable supplies and repairs. Overall, the proposed 2D mu LC-MS/MS instrument will complement the existing proteomics resources on campus and will enhance the current research of NIH-funded users by providing analytical capabilities currently unavailable on campus.